The transfer of genes by means of viruses as a vector is referred to as transduction. Transduction is frequently used to integrate genes into the genome of cells. For example, adeno-associated viruses (AAVs) are used as viruses for this purpose.
AAVs are single-stranded DNA viruses belonging to the Parvorirus family. AAVs require helper viruses, particularly adenoviruses or herpesviruses, for their replication. In the absence of helper viruses AAVs integrate into the host cell genome, particularly at a specific site on chromosome 19.
The genome of AAVs is linear and has a length of about 4680 nucleotides. It comprises two reading frames which code for a structural gene and a non-structural gene. The structural gene is referred to as cap gene. It is controlled by the P40 promoter and codes for three capsid proteins. The non-structural gene is referred to as the rep gene and codes for the rep proteins, Rep 78, Rep 68, Rep 52 and Rep 40. The two former proteins are expressed under the control of the P5 promoter while the expression of Rep 52 and Rep 40 is controlled by the P19 promoter. The functions of the Rep proteins are represented inter alia by the control of replication and transcription of the AAV genome.
It has now been determined that recombinant AAVs, i.e., AAVs containing foreign DNA, often do not integrate into the genome of cells, so that the foreign DNA is not transferred either. However, the latter is important and largely indispensable for manipulating cells, particularly for gene therapy.
It is an object of the present invention to provide a product by which a foreign DNA can be integrated into the genome of cells in an effective manner. According to the invention, this is achieved by the subject matter defined in the claims.